Two specific aims are proposed to test a novel candidate gene, interleukin-four induced gene-1 (IL411), which maps genetically to chromosome 19q13.3-19q13.4, a hotspot for susceptibility to autoimmune diseases, including systemic lupus erythematosus (SLE). IL4I 1 is an attractive candidate because it is regulated by interleukin-four, a key immunomodulatory cytokine, and it is expressed primarily in immune tissues with particular abundance in antigen presenting cells (APCs). Interestingly, IL411 is a lysosomal L-amino acid oxidase (LAAO) that may affect antigen processing/presentation in the MHC class II compartment. If indeed IL4I 1 is associated with SLE susceptibility, then a whole new category of genes that affect the peptide repertoire of APCs may be associated with autoimmune disease susceptibility. In the first aim, the genetic association of IL4I 1 polymorphisms and SLE susceptibility will be examined. IL411 polymorphisms will be identified in SLE patient samples and in public databases of single nucleotide polymorphisms (SNPs). These IL411 polymorphisms will be genotyped in SLE patient and healthy control DNA samples. Differences in genotype or allele frequencies of particular IL411 polymorphisms between SLE patient and healthy control populations will suggest an association with SLE susceptibility. Genotype data will also be stratified to detect possible associations in subsets of patients. Nearby markers and genes in this region will also be tested. In the second aim, differences in polymorphic IL4I1 expression and/or function will be tested. IL4I 1 polymorphisms in noncoding regions will be of particular interest for affecting RNA expression, such as regulation by IL-4, and cell type specific expression. Coding region polymorphisms may affect protein functions such as LAAO activity, lysosomal localization, and antigen processing/presentation. The association of particular IL411 polymorphisms with SLE susceptibility and a difference in IIAI1 expression and/or function could lead to innovative interventions in SLE or other autoimmune diseases that affect the peptide repertoire presented by APCs.